Osteoporosis is a major public health problem for women and men in the United States. The problem of osteoporosis increases as the population ages. Current treatments for osteoporosis, such as dietary calcium supplements, estrogen replacement therapy, bisphosphonates and calcitonin, are largely aimed at decreasing the rate of bone resorption. Bone formation is eventually limited during the use of antiresorptive therapies due to osteoblast/osteoclast coupling. No agent with a primary effect of increasing bone formation, such as fluoride or human parathyroid hormone, is available for therapy. Tetracycline and tetracycline derivatives are known to bind to the mineralization front in bone and are recognized to inhibit osteoclast activity. Tetracyclines, including minocycline, also inhibit the activity of mammalian collagenase and inhibit parathyroid hormone-induced bone resorption in tissue culture. In vivo histomorphometric studies in rodents indicate that minocycline may also increase the rate of bone formation, as well as decrease the rate of bone resorption leading to a net increase in bone mass. To determine if minocycline has direct effects on osteoblast function, we will assess the minocycline effect on the synthesis of skeletal matrix proteins by human osteoblastic cells in vitro. We hypothesize that the administration of minocycline for one year to osteoporotic postmenopausal women at a dose of 200 mg/day with a minimum calcium intake of 800 mg/day and 400 U vitamin D, will induce an increase in bone mineral density with minimal toxicity. This is a placebo-controlled, masked Phase II study that will be expanded if a positive effect on bone density is observed after one year of treatment.